Lancet analyte sensors and methods of manufacturing

ABSTRACT

In some aspects, an analyte sensor is provided for obtaining and detecting an analyte concentration level in a bio-fluid sample. The analyte sensor has a sensor body including a semiconductor material, an active region coupled to the sensor body, and a lancet provided on the analyte sensor. The conductor may include a fiber having a core of a conductive material and a semiconductor cladding surrounding the core. Numerous other aspects are provided.

RELATED APPLICATIONS

This is a continuation of U.S. patent application Ser. No. 13/119,344,now U.S. Pat. No. x,xxx,xxx, filed Mar. 16, 2011 and titled “LANCETANALYTE SENSORS AND METHODS OF MANUFACTURING” (Attorney Docket No.BHDD/002), which claims priority to and is a 371 application ofInternational Application No. PCT/US2009/057253, filed Sep. 17, 2009,titled “LANCET ANALYTE SENSORS AND METHODS OF MANUFACTURING” whichclaims the benefit of U.S. Provisional Patent Application No.61/098,714, filed Sep. 19, 2008 and titled “LANCET ANALYTE SENSORS ANDMETHODS OF MANUFACTURING” (Attorney Docket No. BHDD/002/L), all of whichare hereby incorporated by reference herein in their entireties for allpurposes.

FIELD OF THE INVENTION

The present invention relates to electrochemical analyte sensors thatmay be used to detect an analyte concentration level in a bio-fluidsample taken from a patient.

BACKGROUND OF THE INVENTION

The monitoring of analyte concentration levels in a bio-fluid may be animportant part of health diagnostics. For example, an electrochemicalanalyte sensor may be employed for the monitoring of a patient's bloodglucose level as part of diabetes treatment and care.

An electrochemical analyte sensor may be employed discretely (‘discretemonitoring’), for instance, by detecting an analyte concentration levelin a single sample of blood or other interstitial fluid obtained fromthe patient by a lancet (e.g., by a pin-prick or needle). Optionally,the analyte sensor may be employed continuously (‘continuousmonitoring’), by implanting a sensor in the patient for a duration oftime. In discrete monitoring, there may be a separation between thesample collection process and the measurement of the analyteconcentration level. Typically, after a bio-fluid sample has beenobtained from the patient, such as by the use of a lancet, the samplemay then be transferred to a medium (e.g., a test strip or a detector)for measurement of the sample's analyte concentration level.

Conventional lancets, if too large, may cause undue pain and discomfortto the patient when inserted. Further, because conventionalelectrochemical analyte sensors may be of relatively low sensitivity andtransfer of a bio-fluid sample to the sensor may be relativelyinefficient, a relatively large sample volume may be required in orderto yield an accurate measurement of the analyte concentration level. Insuch instances, if the sample provided is too small, the sensor may beprovided with an insufficient sample volume for an accurate reading.Thus, additional bio-fluid may need to be drawn from the patient.Consequently, lancet insertion may need to be repeated, causing furtherpatient pain and discomfort.

It would therefore be beneficial to provide an analyte sensor adaptedfor bio-fluid analyte monitoring that is minimally invasive duringsample collection, and yet consistently and readily provides foraccurate analyte concentration level measurements from the obtainedbio-fluid sample.

SUMMARY OF THE INVENTION

In an aspect, the present invention provides an analyte sensor,including a sensor body comprised of a semiconductor material; an activeregion coupled to the sensor body; and a lancet formed on an end of theanalyte sensor.

In another aspect, the present invention provides an analyte sensor fordetecting an analyte concentration level in a bio-fluid sample,including a core comprised of a conductive material; a claddingcomprised of a semiconductor material surrounding the core; a cavityformed proximate to the core, and an active region provided within thecavity.

In another aspect, the present invention provides an analyte sensor fordetecting an analyte concentration level in a bio-fluid sample,including a fiber comprised of a semiconductor material; an activeregion in contact with the fiber, and a lancet formed on the analytesensor.

In another aspect, the present invention provides a testing apparatus,including an analyte sensor having a sensor body comprised of asemiconductor material; an active region coupled to the sensor body; anda lancet formed on an end of the analyte sensor.

In a method aspect, the present invention provides a method ofmanufacturing an analyte sensor, including providing a fiber comprisedof a semiconductor material; forming a cavity proximate to the fiber,forming an active region in the cavity, and forming lancet on theanalyte sensor.

Other features and aspects of the present invention will become morefully apparent from the following detailed description, the appendedclaims and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a cross-sectional view of an exemplary embodiment of ananalyte sensor provided according to the present invention.

FIG. 1B is a perspective view of the analyte sensor according to theexemplary embodiment shown in FIG. 1A.

FIG. 2 is a cross-sectional view of an apparatus including anotherexemplary embodiment of an analyte sensor according to the presentinvention.

FIG. 3 is a partial cross-sectional view of an apparatus includinganother exemplary embodiment of an analyte sensor according to thepresent invention.

FIG. 4 is a cross-sectional view of another exemplary embodiment of ananalyte sensor according to the present invention.

FIG. 5 is a cross-sectional view of an apparatus including anotherexemplary embodiment of an analyte sensor according to the presentinvention.

FIG. 6 is a cross-sectional view of an additional exemplary embodimentof an analyte sensor according to the present invention.

FIG. 7A is a cross-sectional view of an additional exemplary embodimentof an analyte sensor according to the present invention.

FIG. 7B is a frontal view of the exemplary embodiment of the analytesensor of FIG. 7A.

FIGS. 8 and 9 are cross-sectional views of additional exemplaryembodiments of analyte sensors according to the present invention.

FIG. 10 is a frontal view of an apparatus including an array of analytesensors according to the present invention.

FIG. 11 is a flowchart illustrating a method of manufacturing lancetanalyte sensors according to the present invention.

DETAILED DESCRIPTION

According to a first aspect of the present invention, a lancet analytesensor is provided that integrates the functions of a lancet and ananalyte sensor into a single device. In this manner, the processes ofsample collection and analyte detection may be performed without theneed to transfer the sample to a transfer medium, such as an analytesensor strip or an external detection or testing device.

An exemplary lancet analyte sensor (hereinafter otherwise referred to asan “analyte sensor” or simply a “sensor”) may include a sensor bodycomprised of a semiconductor material. The sensor body in someembodiments may include a core including a conductive material and acladding. In some embodiments, the conductive core of the analyte sensormay comprise carbon (e.g., graphite) and the semiconductor cladding maycomprise silicon carbide.

In one or more embodiments, a lancet may be formed on the analytesensor. Lancet is defined herein as a sharpened area or point that isprovided on an end of the lancet analyte sensor. For example, in someembodiments, a cladding of the conductor may be cleaved at an angle atone end to provide a lancet for insertion. Optionally, the lancet may bea separate member and may be otherwise coupled to the sensor body, suchas to the cladding for example.

Further, the analyte sensor may include a cavity located proximate tothe sensor body (e.g., proximate the core) for accepting the bio-fluidsample. The term “cavity” as defined herein is a hollow, indented, orconcave area having walls adapted to contain and confine the bio-fluidsample. In some embodiments, the cavity may be at least partiallysurrounded by the cladding whereby the walls of the cavity are formed bythe cladding material (e.g., by an inner surface of the cladding). Inother embodiments, the cavity is at least partially formed by walls of alancet member connected to the sensor body. In further embodiments, thecavity may be formed in a peripheral side wall of the sensor body.Furthermore, the cavity may be provided with an active region which maybe coupled to the core and/or cladding and may be adapted to generate anelectrical current which may be proportional to an analyte concentrationlevel.

The diameter of the lancet analyte sensor may be smaller thanconventional lancets, such that the lancet analyte sensor may beinserted into a patient without causing much, if any, discomfort. Forexample, the sensor body may have an outside diameter of about 150microns or less, about 100 microns or less, about 75 microns or less, oreven about 50 microns or less. Upon insertion, a small volume of thebio-fluid sample (e.g., blood, interstitial fluid, or other body fluid)may be guided into the cavity of the sensor, such as by capillary actionfor example. The required sample volume for an accurate reading mayconstitute less than about 0.4 microliters, less than about 0.3microliters, or even less than about 0.2 microliters, for example. Insome embodiments, the required sample volume may be less than about 0.1microliters, or even less than about 0.05 microliters, for example.

The active region of the lancet analyte sensor may include one or morecatalytic agents and/or reagents adapted to react and convert an analytein a received bio-fluid sample into reaction products from which anelectrical current may be generated. The resulting electrical currentmay flow in the sensor body. For example, the current may flow in thecore and/or the cladding. Thus, in some embodiments, the conductivematerial of the core and/or semiconductor material of the cladding mayform at least a portion of a working electrode. The electrical currentmay then be detected, such as by a measurement or testing device (e.g.,an ammeter) connected to the working electrode, thereby enabling adetermination of an analyte concentration level in the bio-fluid sample.

In operation, the electrical current may have a magnitude, which may becorrelated with the concentration of the analyte in the bio-fluidsample, for example. These and other embodiments of the analyte sensorsof the present invention are described below with reference to FIGS.1A-10.

FIG. 1A is a cross-sectional side view of an exemplary embodiment of alancet analyte sensor 100 provided according to the present invention.The analyte sensor 100 may include a sensor body 102, which may beapproximately cylindrical in shape. The sensor body 102 may furthercomprise a semiconductor material. In particular, the body 102 mayinclude a core 104 comprised of a conductive material. The core 104 maybe at least partially surrounded by a cladding 106, which may becomprised of the semiconductor material. In the exemplary embodimentshown, the cladding 106 may include an annular shape and may fullysurround the core 104, which may comprise the shape of a cylindricalrod. Both the core 104, which may be comprised of a conductive material,and the cladding 106, which may be comprised of semiconductor material,may convey electrical current, albeit the semiconductor material mayhave a higher resistivity as compared to the core 104 and may carry,therefore, less current than the core 104. In some embodiments, the core104 may comprise carbon (e.g. graphite) and the cladding 106 maycomprise silicon carbide (SiC).

In some embodiments, the sensor body may be provided in the form of afiber (e.g., a SiC/C fiber). SiC/C fibers having a suitable SiC claddingand carbon core are manufactured by Specialty Materials Inc. of Lowell,Mass., for example. However, the conductive material of the core 104 maycomprise other conductive materials including graphite, noble metals(e.g., platinum, tantalum, gold or silver) or other conductive metals(e.g., aluminum or copper). The cladding 106 may comprise othersemiconductor materials including Group IV elements such as silicon andgermanium, Group IV compounds such as silicon germanide (SiGe), andGroup III-V compounds such as gallium arsenide (GaAs) and indiumphosphide (InP), among others.

Furthermore, in some embodiments the sensor body 102 may have a totaldiameter D (including the core 104 and cladding 106) of about 150microns or less, about 100 microns or less, about 75 microns or less, oreven about 50 microns or less. The total diameter D may range betweenabout 50 microns and about 150 microns in some embodiments (althoughlarger or smaller sizes may also be used). The core 104 may have adiameter d between about 10 microns and about 100 microns, or evenbetween about 20 microns and about 40 microns. In some embodiments, adiameter d of about 30 microns may be used, although other dimensionsmay also be used. In embodiments in which a SiC cladding 106 is used,the sensor body 102 may be fabricated and machined (e.g., by a laser)easily at small diameters (e.g., less than 150 microns). In addition,the high tensile strength of SiC of between about 3450 MPa to 5865 MPamay provide desirable strength to the sensor body 102. Moreover, even atthis reduced diameter, the sensor body 102 having a SiC cladding 106 mayhave a modulus sufficient to provide flexibility for bending ordeformation and ultimate strength sufficient to prevent breakage duringinsertion.

The sensor body 102 may be cleaved at an angle at one end 108 (the‘cleaved end’) to form a lancet 110 which can be readily inserted into apatient to obtain a bio-fluid sample (e.g., blood, interstitial fluid,or other bodily fluid). Exemplary cleave angles θ range from about 25degrees to about 50 degrees, and are preferably about 35 degrees,although other angles may be used. The cleaved angle may be readily cutby a laser, which may provide a smooth surface finish.

Located proximate to the cleaved end 108 and the core 104 of the sensorbody 102, a cavity 112 may be provided. The cavity 112 may be formed,for example, by removing a portion of the material forming the core 104to produce a hollowed out area. In some embodiments, the cavity 112 mayhave a diameter equivalent to the diameter d of the core 104 (e.g.,about 10 to about 100 microns). However, the diameter of the cavity maybe larger or smaller than the core as well, and may be of irregularshape, such as oval or elongated (in a cross sectional view). The depthh of the cavity 112 may be between about 0.5 mm and about 5 mm, forexample. Other cavity dimensions may be used.

Any suitable technique may be used to remove the core material to formthe cavity 112, such as machining, thermal oxidation (using a torch orlaser), etching, plasma or corona discharge machining, or the like. Insome embodiments, the melting point of the conductive core 104 may bebelow that of the semiconductor cladding 106 thereby enablingpreferential removal of core material without simultaneous removal ofcladding material.

In some embodiments, a channel 114 may be formed in the cladding 106 atthe cleaved end 108 proximate to the lancet 110 such as by deep reactiveetching, for example. The channel 114 may be coupled directly to thecavity 112. Accordingly, during usage, the channel 114 may be in fluidcommunication with the cavity 112 such that during an insertion of thelancet 110 into a patient, at least a portion of the sample bio-fluidcontacting an area located around the lancet 110 may be drawn, such asby capillary action, into the channel 114 and/or may otherwise be guidedinto the cavity 112. In some embodiments, the channel 114 may have awidth of about 10 microns to about 100 microns, and a depth of betweenabout 10 microns to about 100 microns, although other dimensions may beused. The channel may be square or rectangular in cross section, and mayhave rounded corners, for example.

A perspective view of the sensor body 102 including the core 104 andcladding 106 and the cleaved end 108 of the sensor 100 is depicted inFIG. 1B. As illustrated, the channel 114 may be formed into the cleavedend 108 and intersects with the cavity 112. More than one channel 114may also be used. It is noted, however, that the small diameter of thecavity 112 may be sufficient by itself to induce capillary action fordrawing a bio-sample into the cavity 112 without the aid of the channel114. Optionally a vent hole (not shown) may be provided in a side wallof the sensor body. In some embodiments, a sufficient sample forpurposes of detecting an analyte concentration level may have a volumeof less than about 3 microliters, less than about 2 microliters, lessthan about 1 microliters, or even less than about 0.5 microliters. Infurther exemplary embodiments, the relatively small diameter of thesensor body may provide for a sufficient sample volume being less thanabout 0.4 microliters, less than about 0.3 microliters, less than about0.2 microliters, less than about 0.1 microliters, or even less thanabout 0.05 microliters, for example. A sufficient sample volume may, insome embodiments, range between about 0.05 microliters to about 3microliters. Other sample volumes may also be employed. The combinationof the small diameter of the sensor body 102 and the capillary actioninto the cavity 112 may reduce or eliminate much of the pain anddiscomfort associated with bio-fluid sample collection.

Again referring to FIG. 1A, an active region 116 may be positionedwithin the cavity 112, and preferably at the bottom of the cavity,thereby allowing exposure of the active region to the sample bio-fluidthat enters the cavity 112 (e.g., by capillary action). The activeregion 116 may also be positioned in an abutting and/or electricalcontacting relationship with a working electrode 118. The active region116 may include one or more catalytic agents or reagents adapted topromote an electrochemical reaction between an analyte within thebio-fluid sample and the catalytic agents or reagents to producereaction products and the flow of electrons. A portion of the workingelectrode 118 formed proximate to the core 104 may then channel theelectron flow (e.g., through the core 104 and/or cladding 106) andprovide an electrical current which may be proportional to theconcentration of the analyte in the bio-fluid sample. This current maythen be conditioned and displayed in any suitable readout form, such asin a digital readout of a test apparatus (e.g., such as shown in FIG.3).

One group of catalytic agents useful within the active region 116 is theclass of oxidase enzymes which includes, for example, glucose oxidase(which converts glucose), lactate oxidase (which converts lactate), andD-aspartate oxidase (which converts D-aspartate and D-glutamate). Inembodiments in which glucose is the analyte of interest, glucosedehydrogenase (GDH) may optionally be used. Pyrolloquinoline quinine(PQQ) or flavin adenine dinucleotide (FAD) dependent may also be used. Amore detailed list of oxidase enzymes which may be employed in thepresent invention is provided in U.S. Pat. No. 4,721,677, entitled“Implantable Gas-containing Biosensor and Method for Measuring anAnalyte such as Glucose” to Clark Jr. which is hereby incorporated byreference herein in its entirety. Catalytic enzymes other than oxidaseenzymes may also be used.

The active region 116 may include one or more layers (not explicitlyshown) in which the catalytic agents (e.g., enzymes) and/or otherreagents may be immobilized or deposited. The one or more layers maycomprise various polymers, for example, including silicone-based ororganic polymers such as polyvinylpyrrolidone, polyvinylalcohol,polyethylene oxide, cellulosic polymers such as hydroxyethylcellulose orcarboxymethyl cellulose, polyethylenes, polyurethanes, polypropylenes,polyterafluoroethylenes, block co-polymers, sol-gels, etc. A number ofdifferent techniques may be used to immobilize the enzymes in the one ormore layers in the active region 116 including, but not limited to,coupling the enzymes to the lattice of a polymer matrix such as a solgel, cross-linking the agents to a suitable matrix such asglutaraldehyde, electropolymerization or electroactive polymers, andformation of an array between the enzymes via covalent binding, or thelike.

In one or more embodiments, the working electrode 118 may be directlycoupled to the active region 116. In some embodiments, a portion (e.g.,an end surface or pocket) of the conductive core 104 in contact with theactive region 116 may comprise the working electrode 118. In otherembodiments, an electrochemically active layer (not explicitly shown)may be positioned adjacent to the end of the core 104 and/or cladding106 to form the working electrode 118. The electrochemically activelayer may include, for example, noble metals such as platinum,palladium, gold or rhodium, or other suitable materials. In a glucosedetection embodiment, the active layer may undergo a redox reaction withhydrogen peroxide when polarized appropriately. The redox reactioncauses an electrical current to be generated at the working electrode118 by electron transfer that is proportional to the concentration ofthe analyte that has been converted into hydrogen peroxide. This currentmay be conveyed from the electrochemically active layer 116 through thecore 104 and/or cladding 106 to a testing or measurement device (e.g.,such as shown in FIG. 3).

Additionally, in some embodiments of the invention, mediators may beincluded in the active region 116 to promote the conversion of theanalyte to detectable reaction products. Mediators comprise substancesthat act as intermediaries between the catalytic agent and the workingelectrode 118. For example, a mediator may promote electron transferbetween the reaction center where catalytic breakdown of an analytetakes place and the working electrode 118, and may enhanceelectrochemical activity at the working electrode 118. Suitablemediators may include one or more of the following: metal complexesincluding ferrocene and its derivatives, ferrocyanide, phenothiazinederivatives, osmium complexes, quinines, phthalocyanines, organic dyesas well as other substances. In some embodiments, the mediators may becross-linked along with catalytic agents directly to the workingelectrode 118.

The analyte sensor 100 may also include a reference electrode 120, whichin one or more embodiments may also function as a counter electrodeproviding a return path for an electrical current. As described furtherwith reference to FIGS. 1A to 10, the reference electrode may bearranged, formed and/or implemented in a number of different ways. Inthe embodiment depicted in FIG. 1A, the reference electrode 120 maycomprise Ag/AgCl or other suitable electrically conductive materialssuch as carbon, and may be formed as a coil (as shown), foil, film orthe like. In the depicted embodiment, the reference electrode 120 may becoupled to the sensor 100 and may be surrounded by a sealing material122 such as a flexible polymer (e.g., polycarbonate, polyethylene) whichmay be concentric with, and surround, at least a portion of the cladding106 of the sensor body 102. Confined within the sealing material 122 maybe an electrolyte fluid 124 such as a viscous conductive liquid (e.g., ahydrogel) or other salt-containing solution. In some embodiments, thesurface of the cladding 106 may include an insulating layer of anon-permeable polymer (e.g., polyimide, polystyrene) to prevent anelectrical pathway between the electrolyte fluid 124 and the cladding106.

To form an electrochemical cell, the reference electrode 120 may becoupled to the electrolyte fluid 124 contained in the sealing material122. Likewise, the active region 116 of the cavity 112 may be fluidlycoupled to the electrolyte fluid 124 in the sealing material 122 via aconduit 126. The surface area of the reference electrode 120 may beconsiderably larger than the surface area of the working electrode 118to enhance conductivity, and in some embodiments, the surface area ofthe reference electrode 120 may be about 1000 times as large as asurface area of the working electrode 118 or larger. Other referenceelectrode sizes may also be used. An electrical circuit connection tothe reference sensor electrode 120 may be made by any suitable means,such as a conductive strip (not shown) formed along a side of thesensor. Thus, a meter (M) may connect to the reference electrode 120 andthe sensor body 102 and be used to read out an electrical currentgenerated by the active region 116.

FIG. 2 is a cross-sectional view of a testing apparatus includinganother embodiment of a lancet analyte sensor 200 according to thepresent invention. In this embodiment, a sensor body 202, which may havesimilar features to the sensor body 102 described with respect to FIG.1A above, is integral with, and movably coupled to, a housing 213. Forexample, the sensor body 202 may be extended forwardly and retractedbackwardly through a port 211 in the housing 213 (as indicated by theline 207). In some embodiments, the sensor body 202 may be extendedforwardly out of the housing 213 in order to insert the cleaved end 208into the patient and collect a bio-fluid sample in the cavity 212, andthereafter may be retracted backwardly into the housing 213 forpost-sample analysis (e.g., current measurements). The sensor body 202may be coupled to any suitable motion producing mechanism. For example,a motive device 215 may cause relative movement between the housing 213and sensor body 202. The motive device 215 may be a spring whose energymay be released with a trigger mechanism, for example, or an actuatorsuch as a linear motor or solenoid, which is adapted to effectuate suchlinear movement (e.g., extension and retraction).

In some embodiments, the motive device 215 may be electrically coupledto a working electrode 218 of the sensor body 202, such that the motivedevice 215 receives an electrical signal when an analyte is detected inan active region 216 of the sensor 200 and a current is produced at theworking electrode 218. In one or more embodiments, upon receipt of thecurrent signal, the motive device 215 may cause the sensor body 202 toretract into the housing 213. The housing 213 may contain an electrolytefluid 214 (an ‘electrolyte’) such as a salt-containing solution, ahydrogel, or the like.

In operation, the sensor 200 may be in fluid communication with theelectrolyte 214 such that when the body 202 is retracted, the body 202may be at least partially submerged in the electrolyte 214 within thehousing 213. The housing 213 may include a reference electrode 220(e.g., an Ag/AgCl coil or foil or another suitable electricallyconductive reference electrode material) positioned within theelectrolyte fluid 214 and coupled to the sensor 200. In this embodiment,electrochemical activity at the working electrode 218 of the sensor 200may be communicated via a core 204 and/or cladding 206 to theelectrolyte fluid 214 and to the reference electrode 220 when the body202 is retracted into the housing 213 (e.g., upon detection of theanalyte). A current measurement device 219, such as an ammeter (labeled“M”), may be coupled to the reference electrode 220 and workingelectrode 218 to measure the electrical activity representative of theanalyte concentration in the active region 216 of the lancet analytesensor 200.

FIG. 3 is a partial cross-sectional view of another embodiment of alancet analyte sensor 300 according to the present invention. In theembodiment depicted in FIG. 3, a reference electrode 320 may be at leastpartially positioned in a cavity 312 of the lancet sensor 300 where thebio-fluid sample may be received. The electrode 320 may be affixed orotherwise coupled to the cladding 306, for example. In the illustratedembodiment, the reference electrode 320 may be configured as a coil(e.g., of Ag/AgCl or another suitable electrically conductive material).The cavity 312 may be enlarged to accommodate a length of the referenceelectrode 320.

In the illustrated embodiment, contact between the reference electrode320 and an active region 316 and working electrode 318 of the lancetsensor 300 is avoided to ensure proper performance of the lancet sensor300. This may be achieved, for example, by affixing the referenceelectrode 320 to an interior surface of the cavity 312 while maintainingthe reference electrode 320 a clearance distance above the active region316. A suitable electrical connection to the reference sensor may bemade along a side of the sensor 300 (not shown). As in the priorembodiments, the sensor 300 may include a cleaved end 308 formed on thecladding 306 to form an integral lancet 310 and may similarly include acapillary channel 314. In the depicted embodiment, the lancet analytesensor 300 is shown inserted into a port 330 of a testing apparatus 335.Upon insertion into the testing apparatus 335, an electrical contactcomes into direct contact with the core 304 and/or cladding 306.Accordingly, an analyte level proportional to the current in the core304 and/or cladding 306 may be determined and may be displayed on asuitable digital display 340, for example.

FIG. 4 is a cross-sectional view of another embodiment of a lancetanalyte sensor 400 according to the present invention. The lancet sensor400 may include a sensor body 402 including a core 404 including aconductive material surrounded by a cladding 406 including asemiconductor material. In the depicted embodiment, a cavity 412 may beformed in the cladding 406 and may be included proximate the core 404. Alancet 410 may be provided by forming a cleaved end 408 on the sensor400 as in the previous embodiments. Additionally included in thisembodiment may be an insulating layer 409 surrounding the cladding 406.In some embodiments, the core 404 may comprise carbon material (e.g.,graphite) and the cladding 406 may comprise silicon carbide (SiC)although other materials may also be used (as described previously). Thecladding 406 may further comprise a combination of silicon carbide andsilicon nitride (SiC/Si₃N₄) and/or any other suitable semiconductormaterial.

The insulating layer 409 may comprise any suitable dielectric material,such as a polymer. The thickness of the insulating layer 409 should bebetween about 5 microns and about 100 microns, for example. Otherthicknesses may be used. Surrounding the insulating layer 409 may be areference electrode 420 of a conducting material such as Ag/AgCl or anoble metal (e.g., gold, silver, platinum, palladium or the like). Asuitable thickness for the reference electrode 420 may be between about10 microns and about 100 microns, for example. Some embodiments mayinclude a thickness of the insulating layer 409 of between about 30 and70 microns, and a thickness of the reference electrode 420 of betweenabout 10 and 30 microns.

In one or more embodiments of the present invention, the lancet sensorbody 402 may be constructed by first removing carbon material from thecore region near the cleaved end 408 of a SiC/C fiber by suitabletechniques (as described above), to form the cavity 412 and then formingthe insulating layer 409 over the cladding 406.

The cavity 412 may then have applied therein an active region 416. Theactive region 416 may include, as described in the previous embodiments,one or more catalytic agents adapted to promote an electrochemicalreaction of the analyte into reaction products which produces electronflow in a working electrode 418 formed at an upper surface of the core404 within the cavity 412. The core 404 may form a portion of theworking electrode 418 with or without an additional active layer (e.g.,platinum). Moreover, the cladding 406 may form a portion of the workingelectrode as well. By the inclusion of the insulating layer 409surrounding the cladding 406, a reference electrode 420 may be coupledto the outer peripheral surface of the sensor 400 by placement directlyin contact with the insulating layer 409, for example. The referenceelectrode 420 may be made from Ag/AgCl layer or strip, a platinum film,and/or other suitable electrically conductive materials.

FIG. 5 is a cross-sectional view of another embodiment of a testapparatus including another embodiment of a lancet analyte sensor 500.In the depicted apparatus, the lancet analyte sensor 500 and thereference electrode 520 may be mounted in a housing 513. The housing 513may contain an electrolytic fluid 514 such as a hydrogel, and the sensor500 and the reference electrode 520 may be positioned within, andcoupled to each other by, the electrolytic fluid 514. As in theembodiment of FIG. 2, the lancet analyte sensor 500 may be extendablethrough a port 511 in the housing 513 for the purposes of taking abio-fluid sample, and then may be retractable back into the port 511 asillustrated by line 507. As the sensor 500 may be used for samplecollection, it may have a cleaved end 508 formed on the cladding 506 asdescribed above, while the reference electrode 520 need not be used forsample collection, and therefore it need not have a cleaved end. Inaccordance with its sampling function, the sensor 500 may have a cavity512 for receiving a bio-fluid sample containing an analyte, an activeregion 516 coupled to the cavity 512 including one or more catalyticagents or reagents, and a working electrode 518 coupled to the activeregion 516. The working electrode 518 may comprise a portion of the core504 and or cladding 506 of the sensor 500, such as the end surface,which is exposed to the active region 516.

In contrast, the reference electrode 520 need not have a cavity 512, andrather, the end of the conductive core 521 may be directly exposed tothe electrolytic fluid 514 in the housing 513. The exposed core 521 mayact as a reference electrode 520 adapted to detect charge carriersintroduced into the electrolytic fluid 514 from the active region 516 ofsensor 500 because of the sensor's contact with the fluid 514.

FIG. 6 depicts a cross-sectional view of another embodiment of a lancetanalyte sensor 600 according to the present invention. The lancet sensor600 may comprise a core 604 of a conductive material surrounded by acladding 606 of a semiconductor material wherein a cavity 612 may beformed in the cladding and included proximate the core 604. A lancet 610may be provided by forming a cleaved end 608 on the sensor 600, as inthe previous embodiments. The core 604 and the cladding 606 may bemanufactured from the materials as described previously. A referenceelectrode 620 may be coupled to the sensor 600 such as by being providedin the cavity 612 for example, similarly as described with reference toFIG. 3. Other reference electrodes may be employed. In the depictedembodiment, the core 604 may further include a pocket 613 formed thereinwhich may form part of the cavity 612. An active region 616 may beapplied in the pocket 613. Because the pocket 613 may include aconductive material (e.g., graphite) along its sides, an effectivecontact area of the active region 616 in contact with the core 604 maybe enlarged.

FIG. 7A and FIG. 7B depict cross-sectional and frontal views,respectively, of another embodiment of a lancet analyte sensor 700according to the present invention. As in the previous embodiments, thelancet sensor 700 comprises a core 704 comprised of a conductivematerial which may be surrounded by a cladding 706 comprised of asemiconductor material. Similarly, a cavity 712 may be formed in thecladding 706 and may be provided proximate the core 704. A lancet 710may be provided by forming a cleaved end 708 on the cladding 706 andcore 704. The core 704 and the cladding 706 may be manufactured from thematerials described previously. In the depicted embodiment, the cavity712 may be formed in the cladding 706 and the hollowed out area may bedefined by the side walls of the cladding 706. Optionally, a channel 714may be provided along the side of the cladding 706 to aid in the flow ofa bio-fluid sample into the cavity 712. An active region 716 may bepositioned in the cavity 712. The cavity 712 may be any shape such asround, oval, or elongated, and may extend laterally from the surface ofthe cladding 706 to intersect with the core 704 at a bottom of thecavity 712. Providing the cavity 712 along a side surface of the lancetanalyte sensor 700 may minimize blockage of the cavity 712 by perforatedbio-material (e.g., skin) as compared to when the cavity is located atan end of the sensor. Additional cavities (not shown) may be providedalong the side such that additional analytes may be tested.

FIG. 8 is a cross-sectional view of an additional embodiment of a lancetanalyte sensor 800 according to the present invention. As in theprevious embodiments, the lancet sensor 800 may comprise a sensor body802 which may have a core 804 comprised of a conductive materialsurrounded by a cladding 806 comprised of a semiconductor material.Similar to the previous embodiments, a cavity 812 may be formedproximate the core 804. In the depicted embodiment, the cavity 812 maybe at least partially formed by inner walls of a separate lancet member817 which may be coupled to the sensor body 802 by a suitable coupler821 (e.g., by a section of tubing). The lancet member 817 may include anend having a portion that is separated from the body 802 or cleaved atan angle thereby forming an enlarged portion in the cavity adjacent tothe core 804. The enlarged portion may allow additional area forapplying the active region 816. The lancet member 817 may be formed of ahollow SiC fiber or other tubing material, such as stainless steel(e.g., an austenitic stainless steel). An exemplary length of the lancetmember 817 may be about 2 microns to about 5 microns, although otherlengths may be used. A lancet 810 may be provided by forming a cleavedend 808 on the lancet member 817. In this embodiment, the core 804 andthe cladding 806 may be manufactured from the same materials describedpreviously. As in the previous embodiments, the active region 816 may bepositioned in the cavity 812 in contact with the core 804. Although notshown, a reference sensor may be provided on the sensor body 802, forexample.

The embodiment of FIG. 9 illustrates another embodiment of lancetanalyte sensor 900 similar to the sensor of FIG. 8, except that itfurther includes a reference sensor 920 positioned at the end of, andcoupled to, the sensor body 902. Additionally, in some embodiments, thecoupler 921 include at least one vent hole 922.

FIG. 10 illustrates an apparatus including an array of sensors 1000. Thesensors 1000 may be arranged in any configuration, such as in a row orin any three dimensional arrangement (e.g., in a random or orderedpattern). By including multiple sensors 1000 in an array, the overallsignal level may be enhanced, such as for continuous monitoring, forexample. Any of the embodiments of sensors previously described may beincorporated into the array, such as those described with reference toFIG. 1A through FIG. 9.

In another aspect, the present invention provides a method ofmanufacturing an analyte sensor, including providing a fiber comprisedof a semiconductor material; forming a cavity proximate to the fiber,applying an active region in the cavity, and forming lancet on theanalyte sensor.

FIG. 11 illustrates a method of manufacturing an analyte sensoraccording to the present invention. The method 1100 includes a step 1102wherein the fiber is provided including a semiconductor material. Thefiber may be a SiC/C fiber as discussed above. The fiber is provided cutto the appropriate length. A cavity may then be formed proximate thefiber in step 1104. This may be by removal of a portion of the core, bythe formation of a cavity in a side wall of the fiber, or by theattachment of a separate lancet member. An active region may be appliedin contact with the fiber and in the cavity in step 1106 by methodsdescribed above. In step 1108, a lancet may be formed on the analytesensor. Of course, the steps may not be provided in the order shown. Forexample, the step of lancet formation in step 1108 may take place duringthe cutting operation. Likewise, the step of forming a cavity in step1104 may be accomplished after the application of the active region, forexample by adding a separate lancet member. Similarly, the step offorming the active region in the cavity may not occur until theattachment of a separate lancet member.

The foregoing description discloses only exemplary embodiments of theinvention. Modifications of the above disclosed analyte sensors andapparatus incorporating them, which fall within the scope of theinvention, will be readily apparent to those of ordinary skill in theart. Accordingly, while the present invention has been disclosed inconnection with exemplary embodiments thereof, it should be understoodthat other embodiments may fall within the spirit and scope of theinvention, as defined by the following claims.

The invention claimed is:
 1. An analyte sensor, comprising: acylindrical sensor body; an active region positioned within thecylindrical sensor body, the active region configured to determine ananalyte concentration level; and a fluid electrolyte in contact with atleast a portion of the cylindrical sensor body.
 2. The analyte sensor ofclaim 1, wherein the sensor body comprises a core comprising aconductive material and a cladding surrounding the core comprising asemiconductor material.
 3. The analyte sensor of claim 1, furthercomprising a lancet positioned at an end of the cylindrical sensor body.4. The analyte sensor of claim 3, wherein the lancet is formed by acleaved surface at the end of the cylindrical sensor body.
 5. Theanalyte sensor of claim 3, wherein the lancet comprises a separatelancet member coupled to the end of the cylindrical sensor body.
 6. Theanalyte sensor of claim 1, wherein the cylindrical sensor body has acavity extending from an end of the cylindrical sensor body, the activeregion positioned at a bottom of the cavity.
 7. The analyte sensor ofclaim 1, further comprising a reference electrode, wherein the referenceelectrode is coupled to the fluid electrolyte.
 8. The analyte sensor ofclaim 1, wherein the cylindrical sensor body has a conduit and theactive region is fluidly coupled to the fluid electrolyte via theconduit.
 9. The analyte sensor of claim 1, wherein the cylindricalsensor body is configured to extend and retract within a port in ahousing.
 10. An analyte sensor comprising: a cylindrical sensor body; anactive region positioned within the cylindrical sensor body, the activeregion configured to determine an analyte concentration level; and areference electrode coupled to the cylindrical sensor body, wherein thereference electrode comprises a coil, foil, or film.
 11. The analytesensor of claim 10, further comprising a lancet positioned at an end ofthe cylindrical sensor body.
 12. The analyte sensor of claim 10, furthercomprising a sealing material that surrounds the reference electrode andat least a portion of the cylindrical sensor body.
 13. The analytesensor of claim 10, wherein the cylindrical sensor body comprises: acore comprised of a conductive material; a cladding comprised of asemiconductor material surrounding the core; and a cavity formedproximate to the core; wherein: the active region is positioned withinthe cavity.
 14. An analyte sensor comprising: a cylindrical sensor bodyhaving a cavity therein; an active region positioned within the cavity,the active region configured to determine an analyte concentrationlevel; and a reference electrode positioned within the cavity.
 15. Theanalyte sensor of claim 14, wherein a distance separates the referenceelectrode from the active region in the cavity.
 16. The analyte sensorof claim 14, further comprising a lancet positioned at an end of thecylindrical sensor body.
 17. The analyte sensor of claim 14, wherein thecavity includes a pocket formed into a core of the cylindrical sensorbody and the active region is applied in the pocket.
 18. An analytesensor comprising: a cylindrical sensor body comprising: a corecomprised of a conductive material; a cladding comprised of asemiconductor material; and a cavity in the core extending from an endof the cylindrical sensor body; an active region positioned at a bottomof the cavity, the active region configured to determine an analyteconcentration level; and a lancet positioned at the end of thecylindrical sensor body.
 19. The analyte sensor of claim 18, furthercomprising a first electrode in electrical contact with the active areaand the core.
 20. The analyte sensor of claim 19, further comprising: aninsulating layer surrounding the cladding; and a reference electrode atleast partially surrounding the insulating layer.